JPH039106B2 - - Google Patents

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Publication number
JPH039106B2
JPH039106B2 JP56067722A JP6772281A JPH039106B2 JP H039106 B2 JPH039106 B2 JP H039106B2 JP 56067722 A JP56067722 A JP 56067722A JP 6772281 A JP6772281 A JP 6772281A JP H039106 B2 JPH039106 B2 JP H039106B2
Authority
JP
Japan
Prior art keywords
group
formula
compound
hydroxymethyl
oxygen atom
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
JP56067722A
Other languages
Japanese (ja)
Other versions
JPS56167666A (en
Inventor
Dozon Koretsuto
Ansha Jannfuransuwa
Buurujerii Gii
Dosuteru Fuiritsupu
Gyare Patoritsuku
Rakuuru Aran
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Synthelabo SA
Original Assignee
Delalande SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Delalande SA filed Critical Delalande SA
Publication of JPS56167666A publication Critical patent/JPS56167666A/en
Publication of JPH039106B2 publication Critical patent/JPH039106B2/ja
Granted legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/63—Esters of sulfonic acids
    • C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
    • C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C07D263/24—Oxygen atoms attached in position 2 with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/14—Oxygen atoms

Description

【発明の詳細な説明】[Detailed description of the invention]

本発明は抗抑うつ剤として使用される下記一般
式（）の化合物の中間体（原料）として有用な
新規なＮ−アリールオキサゾリジノン、ピロリジ
ノン及びそそららの製造法に関する。なお式
（）の化合物の詳細及び本発明の中間体を用い
た式（）の化合物の製造法については特公昭63
−5391号に記載されている。 〔但しＹは下記ａ），ｂ）のいずれかである。 ａ 酸素原子、但しこの場合Ｘは酸素原子で、Ｂ
はCH2OR6′（R6′は炭素数１〜５の直鎖又は側
鎖アルキル基、シクロヘキシル基又はメトキシ
メチル基）で、またＺ−Ｏ−は炭素数４〜６の
直鎖又は側鎖アルキルオキシ基；アルキル部分
が炭素数４〜７のシクロアルキルメトキシ基；
（１−メチル−１−シクロペンチル）メトキシ
基；２−ブテノキシ基；３−メチル−２−ブテ
ノキシ基；（１−シクロペンテニル）メトキシ
基；（1.シクロヘキセニル）メトキシ基；２−
モルホリノエトキシ基；４−クロロブトキシ
基；（２−オキソ−１−シクロヘキシル）メト
キシ基；２−オキソプロポキシ基；３−シアノ
プロポキシ基；４−シアノブトキシ基；（４−
テトラヒドロピラニル）メトキシ基；（３−テ
トラヒドロピラニル）メトキシ基；式
 The present invention relates to a novel method for producing N-aryloxazolidinone, pyrrolidinone, and sora, which are useful as intermediates (raw materials) for compounds of the following general formula () used as antidepressants. For details of the compound of formula () and the method for producing the compound of formula () using the intermediate of the present invention, see Japanese Patent Publication No. 63
-Described in No. 5391. [However, Y is either a) or b) below. a Oxygen atom, however, in this case X is an oxygen atom, B
is CH2OR6 ' ( R6 ' is a straight chain or side chain alkyl group having 1 to 5 carbon atoms, a cyclohexyl group or a methoxymethyl group), and Z-O- is a straight chain or side chain alkyl group having 4 to 6 carbon atoms. Chain alkyloxy group; cycloalkylmethoxy group in which the alkyl moiety has 4 to 7 carbon atoms;
(1-Methyl-1-cyclopentyl)methoxy group; 2-butenoxy group; 3-methyl-2-butenoxy group; (1-cyclopentenyl)methoxy group; (1.cyclohexenyl)methoxy group; 2-
Morpholinoethoxy group; 4-chlorobutoxy group; (2-oxo-1-cyclohexyl)methoxy group; 2-oxopropoxy group; 3-cyanopropoxy group; 4-cyanobutoxy group; (4-
Tetrahydropyranyl)methoxy group; (3-tetrahydropyranyl)methoxy group; Formula

【式】（R7はＨ、３−Cl、４− Cl、３−Ｆ、４−Ｆ、３−Ｉ、３−Br、３−
CF3、３−NO2、４−NO2、３−CN、４−
CN）のベンジルオキシ基；式
[Formula] (R 7 is H, 3-Cl, 4-Cl, 3-F, 4-F, 3-I, 3-Br, 3-
CF3 , 3- NO2 , 4- NO2 , 3-CN, 4-
Benzyloxy group of CN); formula

【式】【formula】

【式】 又は【formula】 or

【式】 （R8はCl，CN又はNO2，R9はCl又はNO2、ま
たR5はCl又はCN）の二置換ベンジルオキシ
基；又は[Formula] (R 8 is Cl, CN or NO 2 , R 9 is Cl or NO 2 , and R 5 is Cl or CN); or

【式】を表わす。又 は ｂ CH2基、但しこの場合Ｘは酸素原子で、Ｂは
CH2OH基で、またＺはｍ−ニトロベンジル基
を表わすか、或いはＸは２つの水素原子で、Ｂ
はCH2OH基で、またＺはベンジル基を表わ
す。〕 本発明の化合物は下記式 〔但し式中Ａは下記のいずれかである。 ａ 水素原子、但しこの場合Ｙは酸素原子でＢは
式CH2OR′6 （但しR′6は炭素数１−５の直鎖又は側鎖アル
キル基、シクロヘキシル基又はメトキシメチル
基である）の基であるか、又はＹはCH2基でＢ
はヒドロキシメチル基であり、あるいは ｂ ベンジル基、但しこの場合Ｙは酸素原子でＢ
は式CH2OR′6 （但しR′6は上記と同一であるか又はＹがCH2
基でＢがヒドロキシメチル基、エトキシカルボ
ニル基又はカルボキシル基である）の基であ
る。〕 で示されるものである。 下記式 （但しR′6は炭素数１−５の直鎖又は側鎖のア
ルキル基、シクロヘキシル又はメトキシメチル基
である） で示される化合物は、Pd−Ｃ触媒の存在下に、 式 〔但しR′6は式（）と同じである〕 で示される化合物を水添分解して得られる。 式（）の化合物は、式
Represents [formula]. or b CH 2 group, however, in this case X is an oxygen atom and B is
a CH 2 OH group, and Z represents a m-nitrobenzyl group, or X is two hydrogen atoms and B
is a CH 2 OH group, and Z represents a benzyl group. ] The compound of the present invention has the following formula [However, in the formula, A is any of the following. a Hydrogen atom, provided that in this case Y is an oxygen atom and B is of the formula CH 2 OR' 6 (wherein R' 6 is a straight or side chain alkyl group having 1 to 5 carbon atoms, a cyclohexyl group or a methoxymethyl group). group, or Y is a CH 2 group and B
is a hydroxymethyl group, or a benzyl group, in which case Y is an oxygen atom and B
is the formula CH 2 OR′ 6 (where R′ 6 is the same as above or Y is CH 2
B is a hydroxymethyl group, an ethoxycarbonyl group or a carboxyl group). ]. The following formula (However, R'6 is a linear or side chain alkyl group having 1 to 5 carbon atoms, cyclohexyl or methoxymethyl group.) The compound represented by the formula: [However, R′ 6 is the same as the formula ()] It is obtained by hydrogenolyzing the compound represented by the following formula. A compound of formula () has the formula

【式】 〔但しR′6は式（）と同じである〕 のクロルヒドリンをホスゲンで縮合し；次でこの
生成物をパラベンジルオキシアニリンでさらに縮
合し；最後にその生成物をメタノール溶液中でエ
タノール性カリ又はナトリウムメチラートを用い
て環化することから成る三段合成によつて得られ
る。 式 の化合物は、下記式 の化合物を水素化硼素リチウムで還元して得られ
る式 の化合物をPd−Ｃ触媒の存在下に水添分解して
得られる。 式（）の化合物は、パラベンジルオキシア
ニリンをイタコン酸で縮合して得られる式 の化合物を硫酸の存在下にエタノールでエステル
化して得られる。 実施例 １ 第１工程： ３−ｐ−ベンジルオキシフエニル−５−イソプ
ロピルオキシメチル−２−オキサゾリジノン
〔〕 コード番号： 225 560mlのジクロルエタンと59ｇのホスゲンの溶
液に83.4ｇの１−クロル−３−イソプロピルオキ
シ−２−プロパノール（）を添加し、30分間で
81.9ｇのＮ，Ｎ−ジエチルアニリンと160mlのジ
クロルエタンの溶液を添加した。前記混合物を50
℃で２時間加熱し、水250mlを加え、有機層をデ
カントし、217.5ｇのｐ−ベンジルオキシアニリ
ンを30分間で添加した。その混合物を３時間還流
し過し、1N塩酸溶液と水で洗い、乾燥し溶剤
を蒸発して残留物をエタノールに再結晶させた。
165.5ｇの製品を得た。 収 率：81％ 融 点：107℃ NMRスペクトル：δppm（DMSO） 9.80，Ｓ，−NH−COO− １プロトン 7.40，Ｓ，及び5.08，Ｓ： ７プロトン 7.18，ｍ，芳香族プロトン ４プロトン 5.20，ｍ，Chlorhydrin of [formula] [where R′ 6 is the same as formula ()] is condensed with phosgene; then this product is further condensed with parabenzyloxyaniline; finally the product is dissolved in methanol solution. Obtained by a three-step synthesis consisting of cyclization with ethanolic potassium or sodium methylate. formula The compound has the following formula The formula obtained by reducing the compound with lithium borohydride is obtained by hydrogenolyzing the compound in the presence of a Pd-C catalyst. The compound of formula () is obtained by condensing parabenzyloxyaniline with itaconic acid. is obtained by esterifying the compound with ethanol in the presence of sulfuric acid. Example 1 First step: 3-p-Benzyloxyphenyl-5-isopropyloxymethyl-2-oxazolidinone [] Code number: 225 83.4 g of 1-chloro-3- in a solution of 560 ml of dichloroethane and 59 g of phosgene. Add isopropyloxy-2-propanol () for 30 minutes.
A solution of 81.9 g N,N-diethylaniline and 160 ml dichloroethane was added. 50% of the mixture
Heated at <0>C for 2 hours, added 250 ml of water, decanted the organic layer and added 217.5 g of p-benzyloxyaniline over 30 minutes. The mixture was filtered under reflux for 3 hours, washed with 1N hydrochloric acid solution and water, dried, the solvent was evaporated and the residue was recrystallized in ethanol.
165.5g of product was obtained. Yield: 81% Melting point: 107℃ NMR spectrum: δppm (DMSO) 9.80, S, -NH-COO- 1 proton 7.40, S, and 5.08, S: 7 protons 7.18, m, aromatic proton 4 protons 5.20, m,

【式】 １プロトン 3.85，ｄ，（Ｊ＝５Hz）−CH2−Ｏ−
２プロトン 3.59，ｍ，Cl−CH2−CH− ３プロトン 1.06，ｄ，[Formula] 1 proton 3.85, d, (J=5Hz) -CH 2 -O-
2 protons 3.59, m, Cl-CH 2 -CH- 3 protons 1.06, d,

【式】 ５プロトン IRスペクトル：バントNH−COO：1700及び
3305cm-1 この化合物165.5ｇと29.3ｇのカリを2.4のエ
タノールに溶解した液を３時間50℃に加熱した。
その後溶剤を蒸発し残留物をクロロホルムに抽出
し、水洗いし、乾燥して溶剤を蒸発させた。残留
物をエーテル中で結晶させ、又ジオキサン中で再
結晶した。113ｇの製品を得た。 収 率：75％ 融 点：110℃ 実験式 ：C20H23NO4 分子量 ：341.3 元素分析：[Formula] 5 proton IR spectrum: Band NH-COO: 1700 and
3305 cm -1 A solution of 165.5 g of this compound and 29.3 g of potash in 2.4 parts of ethanol was heated to 50°C for 3 hours.
Thereafter, the solvent was evaporated and the residue was extracted into chloroform, washed with water, dried and the solvent was evaporated. The residue was crystallized in ether and recrystallized in dioxane. 113g of product was obtained. Yield: 75% Melting point: 110℃ Empirical formula: C 20 H 23 NO 4 Molecular weight: 341.3 Elemental analysis:

【表】 同一方法で、但し相当する試薬から、表(1)に示
すコード番号226−229を付した式（）の化合物
を製造した。 第２工程： ３−ｐ−ヒドロキシフエニル−５−イソプロピ
ルオキシメチル−２−オキサゾリジノン（） コード番号：221 第１工程で製造した化合物85ｇを1700mlのジオ
キサンと15mlの6.5N塩酸性アルコールに溶解し
た液を、8.5ｇの10％Pd−Ｃ触媒の存在下に、オ
ートクレーブで６Kgの圧力下に５時間水添分解し
た。次で、前記混合物を過し、溶剤を蒸発し、
残留物をエーテル中に結晶させ、又トルエン中で
再結晶させた。43.7ｇの製品を得た。 収 率：70％ 融 点：93℃ 実験式 ：C13H17NO4 分子量 ：251.3 元素分析：[Table] Compounds of formula () with code numbers 226-229 shown in Table (1) were prepared in the same manner but from corresponding reagents. 2nd step: 3-p-hydroxyphenyl-5-isopropyloxymethyl-2-oxazolidinone () Code number: 221 85 g of the compound produced in the 1st step was dissolved in 1700 ml of dioxane and 15 ml of 6.5N hydrochloric alcohol. The liquid was hydrogenolyzed in an autoclave under a pressure of 6 Kg for 5 hours in the presence of 8.5 g of 10% Pd-C catalyst. then filtering the mixture and evaporating the solvent;
The residue was crystallized in ether and recrystallized in toluene. 43.7g of product was obtained. Yield: 70% Melting point: 93℃ Empirical formula: C 13 H 17 NO 4 Molecular weight: 251.3 Elemental analysis:

【表】 同一方法で、但し相当する試薬から、表に示
すコード番号222−224および230−232を付した、
式（）の化合物を製造した。 実施例 ２ １−Ｎ−ｐ−ベンジルオキシフエニル−４−ヒ
ドロキシメチル−２−ピロリジノン（） 第１工程： 〔（Ｎ−ｐ−ベンジルオキシフエニル−２−ピ
ロリジノン）−４−イル〕カルボン酸（） イタコン酸46ｇとｐ−ベンジルオキシアニリン
70ｇと400mlの水との混合物を還流し、フイルタ
ー上でクロロホルムで洗つて乾燥し、アセトン中
で再結晶させた。製品77ｇを得た。 収 率：71％ 融 点：194℃ 実験式 ：C13H17NO4 分子量 ：311.32 元素分析：[Table] Using the same method, but from corresponding reagents, with the code numbers 222-224 and 230-232 shown in the table,
A compound of formula () was prepared. Example 2 1-N-p-benzyloxyphenyl-4-hydroxymethyl-2-pyrrolidinone () 1st step: [(N-p-benzyloxyphenyl-2-pyrrolidinone)-4-yl]carboxylic acid () 46g of itaconic acid and p-benzyloxyaniline
A mixture of 70 g and 400 ml of water was refluxed, washed with chloroform on a filter, dried and recrystallized in acetone. 77g of product was obtained. Yield: 71% Melting point: 194℃ Empirical formula: C 13 H 17 NO 4 Molecular weight: 311.32 Elemental analysis:

【表】 第２工程： 〔（２−Ｎ−ｐ−ベンジルオキシフエニルピロ
リジノン）−４−イル〕エチルカルボキシレー
ト（〕 第１工程で得た酸84ｇを400mlのエタノールと
６mlの濃硫酸に溶解した液を２時間還流した。つ
いで、それを冷却し、沈殿物を過し、水洗い
し、乾燥してイソプロパノール中に再結晶させ
た。47ｇの製品を得た。 収 率：51％ 融 点：106℃ 実験式 ：C20H21NO4 分子量 ：339.38 元素分析：[Table] Second step: [(2-N-p-benzyloxyphenylpyrrolidinone)-4-yl]ethylcarboxylate () Dissolve 84 g of the acid obtained in the first step in 400 ml of ethanol and 6 ml of concentrated sulfuric acid. The solution was refluxed for 2 hours. Then it was cooled and the precipitate was filtered, washed with water, dried and recrystallized in isopropanol. 47 g of product was obtained. Yield: 51% Melting point: 106℃ Empirical formula: C 20 H 21 NO 4 Molecular weight: 339.38 Elemental analysis:

【表】 第３工程： 1N−ｐ−ベンジルオキシフエニル−４−ヒド
ロキシメチル−２−ピロリジノン（） 7.9ｇのナトリウムボロハイドライドと18ｇの
臭化リチウムと400mlのジグリムの混合物に、先
の工程で製造した化合物を70ｇ添加した。つい
で、前記混合物を50分間で100℃に加熱し、500ｇ
の氷と50mlの濃塩酸に稀釈し、クロロホルムで抽
出した。溶剤を蒸発し、残留物をイソプロピルエ
ーテル中で結晶させ、トルエン中に再結晶させ
た。45ｇの製品を得た。 収 率：72％ 融 点：110℃ 実験式 ：C18H19NO3 分子量 ：297.34 元素分析：[Table] 3rd step: 1N-p-benzyloxyphenyl-4-hydroxymethyl-2-pyrrolidinone () Added in the previous step to a mixture of 7.9 g of sodium borohydride, 18 g of lithium bromide and 400 ml of diglyme. 70g of the manufactured compound was added. The mixture was then heated to 100°C for 50 minutes and 500 g
of ice and 50 ml of concentrated hydrochloric acid, and extracted with chloroform. The solvent was evaporated and the residue was crystallized in isopropyl ether and recrystallized in toluene. 45g of product was obtained. Yield: 72% Melting point: 110℃ Empirical formula: C 18 H 19 NO 3 Molecular weight: 297.34 Elemental analysis:

【表】【table】

【表】【table】

【表】【table】

Claims (1)

【特許請求の範囲】 １ 式 〔但し式中Ａは下記のいずれかである。 ａ 水素原子、但しこの場合Ｙは酸素原子で、Ｂ
は式CH2OR6′（但しR6′は炭素数１〜５の直鎖
又は側鎖アルキル基、シクロヘキシル基又はメ
トキシメチル基である）の基であるか、又はＹ
はCH2基でＢはヒドロキシメチル基であり、あ
るいは ｂ ベンジル基、但しこの場合Ｙは酸素原子で、
Ｂは式CH2OR6′（但しR6′は上記と同一である）
の基であるか、又はＹがCH2基でＢはヒドロキ
シメチル基、エトキシカルボニル基又はカルボ
キシル基である。）〕 で示される化合物。 ２ Ａが水素原子、Ｙが酸素原子、そしてＢが式
CH2OR6′（但しR6′は炭素数１〜５の直鎖又は側
鎖アルキル基、シクロヘキシル基又はメトキシメ
チル基である）の基である特許請求の範囲第１項
記載記載の化合物。 Ｃ Ａが水素原子、ＹがCH2基、そしてＢがヒド
ロキシメチル基である特許請求の範囲第１項記載
の化合物。 ４ Ａがベンジル基、Ｙが酸素原子、そしてＢが
式CH2OR6′（但しR6′は炭素数１〜５の直鎖又は
側鎖アルキル基、シクロヘキシル基又はメトキシ
メチル基である）の基である特許請求の範囲第１
項記載の化合物。 ５ Ａがベンジル基、ＹがCH2基、そしてＢがヒ
ドロキシメチル、エトキシカルボニル及びカルボ
キシルから成る群から選ばれる特許請求の範囲第
１項記載の化合物。[Claims] 1 formula [However, in the formula, A is any of the following. a Hydrogen atom, however, in this case Y is an oxygen atom, B
is a group of the formula CH 2 OR 6 ′ (wherein R 6 ′ is a straight chain or side chain alkyl group having 1 to 5 carbon atoms, a cyclohexyl group or a methoxymethyl group), or Y
is CH 2 group and B is hydroxymethyl group, or b benzyl group, but in this case Y is oxygen atom,
B is the formula CH 2 OR 6 ′ (where R 6 ′ is the same as above)
or Y is a CH 2 group and B is a hydroxymethyl group, an ethoxycarbonyl group or a carboxyl group. )] A compound represented by 2 A is a hydrogen atom, Y is an oxygen atom, and B is a formula
The compound according to claim 1, which is a group of CH 2 OR 6 ' (wherein R 6 ' is a linear or side chain alkyl group having 1 to 5 carbon atoms, a cyclohexyl group or a methoxymethyl group). The compound according to claim 1, wherein CA is a hydrogen atom, Y is a CH 2 group, and B is a hydroxymethyl group. 4 A is a benzyl group, Y is an oxygen atom, and B is of the formula CH 2 OR 6 ' (wherein R 6 ' is a straight chain or side chain alkyl group having 1 to 5 carbon atoms, a cyclohexyl group or a methoxymethyl group). Claim 1 which is the basis of
Compounds described in Section. 5. A compound according to claim 1, wherein A is a benzyl group, Y is a CH2 group, and B is selected from the group consisting of hydroxymethyl, ethoxycarbonyl, and carboxyl.
JP6772281A 1978-06-09 1981-05-07 N-aryloxazolidinone, pyrrolidinone and their manufacture Granted JPS56167666A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR7817388A FR2428032A1 (en) 1978-06-09 1978-06-09 N-Aryl-azolidone cpds. - useful as psychotropic agents and antidepressants (NL 11.12.79)

Publications (2)

Publication Number Publication Date
JPS56167666A JPS56167666A (en) 1981-12-23
JPH039106B2 true JPH039106B2 (en) 1991-02-07

Family

ID=9209330

Family Applications (2)

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JP7295479A Granted JPS5551064A (en) 1978-06-09 1979-06-09 Novel aryloxazolidinone*oxazolidinethione* pyrrolidinone*pyrrolidine and thiazolidinone* their manufacture and their therapeutic application
JP6772281A Granted JPS56167666A (en) 1978-06-09 1981-05-07 N-aryloxazolidinone, pyrrolidinone and their manufacture

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Application Number Title Priority Date Filing Date
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Country Status (3)

Country Link
JP (2) JPS5551064A (en)
FR (1) FR2428032A1 (en)
ZA (1) ZA792799B (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2506769A2 (en) * 1978-06-09 1982-12-03 Delalande Sa Cyano:pentyl:phenyl-methoxymethyl-oxazolidinone - useful as antidepressant
FR2458547B2 (en) * 1978-06-09 1986-05-16 Delalande Sa NOVEL AZOLONES N-ARYLE, THEIR PREPARATION PROCESS AND THEIR THERAPEUTIC APPLICATION
FR2500450A1 (en) * 1981-02-25 1982-08-27 Delalande Sa NOVEL AMINOMETHYL-5-OXAZOLIDINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THERAPEUTIC USE THEREOF
FR2528046B1 (en) * 1982-06-08 1985-06-21 Delalande Sa OPTICALLY ACTIVE OXAZOLIDINONE-2 N-ARYLATED DERIVATIVES, SPECIFIC AND REVERSIBLE INHIBITORS OF TYPE B MONOAMINE OXYDASE AND PROCESS FOR THEIR PREPARATION
JPS608277A (en) * 1983-06-07 1985-01-17 ザ・デュポン・メルク・ファーマシュウティカル・カンパニー Aminomethyloxooxazolidinylbenzene derivative
FR2609029B1 (en) * 1986-12-30 1989-12-08 Delalande Sa 5-AMINOETHYL DERIVATIVES OF OXAZOLIDINONE-2, THEIR PREPARATION PROCESS AND THEIR THERAPEUTIC APPLICATION
CA1302422C (en) * 1986-09-03 1992-06-02 Margherita Strolin-Benedetti 5-aminoethyloxazolidin-2-one derivatives, process for the preparation thereofand their therapeutic use
FR2603279B1 (en) * 1986-09-03 1988-12-16 Rech Ind BENZYLOXY-PHENYL-OXAZOLIDINONES, METHOD OF PREPARATION AND USE IN THERAPEUTICS
JPWO2007116960A1 (en) * 2006-04-06 2009-08-20 財団法人乙卯研究所 Oxazolidinone derivatives having carbocyclic rings

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3655687A (en) * 1969-03-18 1972-04-11 Delalande Sa Derivatives of 5-hydroxymethyl-3-substituted-2-oxazolidinones process of preparation thereof and therapeutic application

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1602544A (en) * 1968-10-29 1970-12-21 Acetylenic 2-oxazolidinones
CH618682A5 (en) * 1975-11-07 1980-08-15 Ciba Geigy Ag

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3655687A (en) * 1969-03-18 1972-04-11 Delalande Sa Derivatives of 5-hydroxymethyl-3-substituted-2-oxazolidinones process of preparation thereof and therapeutic application

Also Published As

Publication number Publication date
JPS635391B2 (en) 1988-02-03
FR2428032A1 (en) 1980-01-04
ZA792799B (en) 1980-08-27
JPS56167666A (en) 1981-12-23
JPS5551064A (en) 1980-04-14
FR2428032B1 (en) 1981-10-16

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